Multienzyme System in Amorphous Metal–Organic Frameworks for Intracellular Lactate Detection

Lactate is an important downstream product of glycolysis in living cells, and its level is highly related with diseases. On the basis of amorphous metal–organic frameworks (aMOFs), a multienzyme system consisting of lactate oxidase (LOx) and horseradish peroxidase (HRP) was established for intracellular lactate detection. By coencapsulation in aMOFs with proximity, LOx and HRP were delivered into cells, serving as artificially constructed organelles, exhibiting high activity and selectivity for the intracellular detection of the important metabolite lactate, which improved the signal to noise ratio by ∼650-fold. As demonstrated by both experimental and simulation results, the high efficiency was attributed to the short distance between the two types of enzymes coencapsulated in aMOFs. The concept of constructing multienzyme systems in this study shows promise for the detection of various intracellular metabolites

DataSheet2_Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer.xlsx

Background: Numerous reports have highlighted that the tumor microenvironment (TME) is closely linked to survival outcome and therapeutic efficacy. However, a comprehensive investigation of the TME feature in breast cancer (BC) has not been performed.Methods: Here, we performed consensus clustering analysis based on TME cell expression profiles to construct TME pattern clusters and TME-related gene signature in BC. GSVA combined with CIBERSORT and ssGSEA algorithms were applied to evaluate the differences in biological pathway and immune cell infiltration level, respectively. The PCA method was employed to construct TME-score to quantify the TME-mediated pattern level in individual BC patients.Results: We determined two distinct TME gene clusters among 3,738 BC samples, which exhibited distinct survival outcome and enriched biological processes. The TME features demonstrated that these two clusters corresponded to the established immune profiles: hot and cold tumor phenotypes, respectively. Based on TME-related signature genes, we constructed the TME-score and stratified BC patients into low and high TME-score groups. Patients with high TME-score exhibited favorable outcome and increased infiltration of immune cells. Further investigation revealed that high TME-score was also related with high expression of immunosuppressive molecules, decreased tumor mutation burden (TMB), and high rate of mutation in significantly mutated genes (SMGs) (e.g., PIK3CA and CDH1).Conclusion: Assessing the TME-mediated pattern level of individual BC patients will assist us in better understanding the responses of BC patients to immunotherapies and directing more effective immunotherapeutic approaches.</p

DataSheet1_Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer.docx

Background: Numerous reports have highlighted that the tumor microenvironment (TME) is closely linked to survival outcome and therapeutic efficacy. However, a comprehensive investigation of the TME feature in breast cancer (BC) has not been performed.Methods: Here, we performed consensus clustering analysis based on TME cell expression profiles to construct TME pattern clusters and TME-related gene signature in BC. GSVA combined with CIBERSORT and ssGSEA algorithms were applied to evaluate the differences in biological pathway and immune cell infiltration level, respectively. The PCA method was employed to construct TME-score to quantify the TME-mediated pattern level in individual BC patients.Results: We determined two distinct TME gene clusters among 3,738 BC samples, which exhibited distinct survival outcome and enriched biological processes. The TME features demonstrated that these two clusters corresponded to the established immune profiles: hot and cold tumor phenotypes, respectively. Based on TME-related signature genes, we constructed the TME-score and stratified BC patients into low and high TME-score groups. Patients with high TME-score exhibited favorable outcome and increased infiltration of immune cells. Further investigation revealed that high TME-score was also related with high expression of immunosuppressive molecules, decreased tumor mutation burden (TMB), and high rate of mutation in significantly mutated genes (SMGs) (e.g., PIK3CA and CDH1).Conclusion: Assessing the TME-mediated pattern level of individual BC patients will assist us in better understanding the responses of BC patients to immunotherapies and directing more effective immunotherapeutic approaches.</p

Determination of olaquindox, carbadox and cyadox in animal feeds by ultra-performance liquid chromatography tandem mass spectrometry

<p>Olaquindox, carbadox, and cyadox are chemically synthesised antibacterial and growth-promoting agents for animals. At high doses they may exert mutagenicity and hepatic and adrenal toxicities in animals. Regrettably, these substances are frequently abused or misused when added into animal feeds. Thus, developing a sensitive and reliable method for simultaneous determination of olaquindox, carbadox, and cyadox in different kinds of animal feeds is crucially important for food safety monitoring. In this paper we optimised instrumental conditions, extraction solvents, solid phase extraction cartridges, and pH of the loading solvents on the Oasis HLB cartridge. Under the optimal conditions, mean recoveries ranged from 74.1 to 111%, and intra-day and inter-day variations were lower than 14.6% and 10.8%, respectively. The limits of quantification for olaquindox, carbadox, and cyadox were 0.05 mg kg⁻¹, 0.10 mg kg⁻¹, and 0.025 mg kg⁻¹, respectively. The proposed method uses ultra-performance liquid chromatography tandem mass spectrometry and is sensitive and reliable for the simultaneous determination of olaquindox, carbadox, and cyadox in three kinds of animal feeds (specifically, mixed feed, concentrated feed, and additive premixed feed). This method has good precision, high sensitivity, and good reproducibility, and thus it can be used for convenient and accurate determination of olaquindox, carbadox, and cyadox in different kinds of animal feeds.</p

Optimization of Operating Parameters for Low NO_<i>x</i> Emission in High-Temperature Air Combustion

This paper focuses on determining the effects of operating parameters on NO_<i>x</i> emission and parameters optimization to reduce NO_<i>x</i> emission for high-temperature air combustion furnaces. For this purpose, the Taguchi method, based on computational fluid dynamics (CFD) modeling, was implemented. Eight factors were considered, including the velocity of air injection (A), the velocity of fuel injection (B), the oxygen concentration in preheated air (C), the preheated air temperature (D), fuel temperature (E), the interaction between A and B, the interaction between A and C, and the interaction between A and D. An L₂₇ (3¹³) orthogonal array was employed to arrange the CFD modeling tests. By analysis of variance, the degrees of effect of the selected factors are determined, which are as follows, in descending order: E, B, C, A, D, AB, AC, and AD. The major factors are found to be A, B, C, and E, while the other factors are considered to be secondary factors. The optimal operating conditions are determined to be A = 120 m/s, B = 85 m/s, C = 18.5%, D = 1493 K, and E = 298 K. Under the optimal operating condition, the concentration of NO_<i>x</i> emission decreases by 25.45%, compared with the original operating condition

MOESM1 of An AIDS patient with urine retention

Additional file 1. Chest CT in Oct 2017

MOESM2 of An AIDS patient with urine retention

Additional file 2. Prostate CT after 6 month of anti-fungal treatment

Dual-Recognition Triggered Proximity Ligation Combined with a Rolling Circle Amplification Strategy for Analysis of Exosomal Protein-Specific Glycosylation

Exosomal surface glycan reveals the biological function and molecular information on the protein, especially in indicating the pathogenesis of certain diseases through monitoring of specific protein glycosylation accurately. However, in situ and nondestructive measurement techniques for certain Exosomal glycoproteins are still lacking. In this work, combined with on-chip purification, we designed a proximity ligation assay-induced rolling circle amplification (RCA) strategy for highly sensitive identification of Exosomal protein-specific glycosylation based on a couple of proximity probes to target Exosomal protein and the protein-specific glycosylation site. Benefiting from efficient separation, scalable dual-recognition, and proximity-triggered RCA amplification, the proposed strategy could convert different protein-specific glycan levels to prominent changes in absorbance signals, resulting in accurate quantification of specific glycosylated Exosomal protein. When detecting the glycosylated PD-L1 on MDA-MB-231 exosomes and glycosylated PTK7 on HepG2 exosomes, the detection limits were calculated to be as low as 1.04 × 104 and 2.759 × 103 particles/mL, respectively. In addition, we further expand the dual-recognition site to investigate the potential correlation of Exosomal glycosylation with polarization of THP-1 cells toward the tumor-suppressive M1 phenotype. Overall, this strategy provides a universal tool for multiple analyses of diverse protein-specific glycosylated exosomes, exhibiting enormous potential to explore exosome function and search for new early diagnosis markers

Video_1_Case report: Recurrent hemobilia due to hepatic artery pseudoaneurysm mimicking gastrointestinal tract bleeding.MP4

Hemobilia, a rare form of upper gastrointestinal bleeding (UGIB), is a potentially fatal complication that usually occurs after iatrogenic hepatobiliary trauma. However, hemobilia is clinically challenging to diagnose and often gets too late to diagnose. We herein report a case of recurrent hemobilia due to hepatic artery pseudoaneurysm (HAP) that was initially misdiagnosed as gastrointestinal tract bleeding. However, the patient was treated successfully with percutaneous coil occlusion of the pseudoaneurysm. This case illustrates that hemobilia can present as a mimic of gastrointestinal tract bleeding, but this is often difficult to diagnose at first glance and often misleads clinicians, especially emergency physicians, into making an incorrect diagnosis. Familiarity with the clinical features of hemobilia can help raise clinical suspicion and facilitate the early diagnosis and treatment of hemobilia.</p

Data_Sheet_1_Comprehensive assessment of emergency departments in county-level public hospitals: a multicenter descriptive cross-sectional study in Henan province, China.docx

BackgroundEmergency Departments (EDs) play a crucial role in providing immediate medical care, particularly in densely populated countries like China. While previous research has predominantly focused on well-funded urban hospitals, this study offers a comprehensive evaluation of EDs in county-level public hospitals in Henan province, China, aiming to identify disparities and challenges.MethodsA descriptive cross-sectional survey was conducted in 382 public hospitals across Henan province, China, from July 1, 2023, to August 1, 2023. Data were collected using an electronic questionnaire covering hospital information, human resources, infrastructure, clinical capabilities, and operational capacities. The data collection period for this survey spanned from January 1 to December 31, 2022.ResultsWith a remarkable 94.0% response rate, our study reveals significant disparities in county-level public hospitals compared to their provincial or municipal counterparts in Henan Province, China. County-level hospitals, which constitute 266 of the total 342 surveyed facilities, exhibit notable differences, including fewer doctors (median: 11 vs. 23, p ConclusionWhile provincial or municipal hospitals enjoy better resources, county-level hospitals, especially crucial in less urbanized regions, face substantial challenges. Addressing these disparities is imperative, necessitating targeted investments, improved infrastructure, enhanced clinical training, and the adoption of innovations like telemedicine to enhance the quality of emergency care.</p